Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/177658
Title: Vanadate stimulates system A amino acid transport activity in skeletal muscle. Evidence for the involvement of intracellular pH as a mediator of vanadate action
Author: Muñoz Moruno, Purificación
Gumà i Garcia, Anna Maria
Camps Camprubí, Marta
Furriols Espona, Marc
Testar, Xavier
Palacín Prieto, Manuel
Zorzano Olarte, Antonio
Keywords: Aminoàcids
Músculs
Farmacologia
Metabolisme
Amino acids
Muscles
Pharmacology
Metabolism
Issue Date: 25-May-1992
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: Sodium orthovanadate caused a 2-fold stimulation of system A transport activity in soleus muscle, as assessed by the uptake of the nonmetabolizable analog 2-(methylamino)isobutyric acid (MeAIB). The effect of vanadate on system A was rapid, concentration-dependent and was characterized by an increased Vmax without modification of Km for MeAIB. Under these conditions, vanadate also activated 3-O-methylglucose uptake and lactate production. The effects of vanadate on muscle metabolism showed a complex interaction with the effects of insulin. Thus, the stimulatory effects of vanadate and insulin on MeAIB and 3-O-methylglucose uptake were not additive; however, the effects of insulin and vanadate on lactate production were additive. In spite of the lack of additivity, insulin- and vanadate-induced stimulation of system A differed in their sensitivity to gramicidin D, being the vanadate effect more susceptible to inhibition by gramicidin D than the insulin effect. System A transport activity shows a dependence on pH, and recent results suggest the presence of critical histidine residues on the A carrier that may be responsible for its pH dependence (Bertran, J., Roca, A., Pola, E., Testar, X., Zorzano, A. & Palacín, M. (1991) J. Biol. Chem. 266, 798-802). In this regard, a rise in extracellular pH led to a substantial activation of system A. Furthermore, lowering of muscle intracellular pH induced by ethylisopropylamiloride (EIPA), a specific inhibitor of sodium/proton exchange activity, led to inhibition of system A. This suggests that critical histidine residues are present in an intracellular localization on the A carrier. Furthermore, the rate of muscle glycolysis was also altered in response to a rise in extracellular pH or to EIPA treatment. Regarding the mechanisms involved in vanadate action, vanadate treatment in the incubated soleus muscle did not cause any significant stimulation of tyrosine kinase activity after partial purification of muscle insulin receptors. On the other hand, vanadate but not insulin caused a substantial increase in muscle intracellular pH as assessed by 5,5'-dimethyloxazolidine-2,4-dione equilibrium. This effect of vanadate on intracellular pH was not due to activation of the sodium/proton exchanger, since it was not blocked by EIPA. Based on these findings, we suggest that alkalinization of muscle intracellular pH might mediate the effects of vanadate on system A and on glycolysis.
Note: Reproducció del document publicat a: https://www.jbc.org/issue/S0021-9258(19)X5001-2
It is part of: Journal of Biological Chemistry, 1992, vol. 267, num. 15, p. 10381-10388
URI: https://hdl.handle.net/2445/177658
ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Ciències Fisiològiques)

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